Studies are conducted to define the mechanisms involved in tumor growth and metastasis and to develop new animal models of human cancers. We have found that a basement membrane extract (Matrigel) when premixed with human tumor cells (which do not grow well in mice) promotes their incidence and growth. We have been able to culture new highly differentiated human tumor cell lines from the tumors grown in mice including certain colon cell lines. Laminin, a major basement membrane component, has been found to promote the malignant phenotype. Selection for adhesion to laminin was carried out with a human colon cancer cell line developed from a patient biopsy passaged in mice with Matrigel and the adherent cells were found to be highly malignant when injected with Matrigel. The laminin non-adherent cells formed few tumors which were highly differentiated. Various biologically active laminin-derived synthetic peptides have been identified. Previously, we found that YIGSR (tyr-ile-gly-ser-ag) reduced tumor growth, metastases and angiogenesis. We now find multimeric forms of this peptide are more active than the monomers and are able to induce apoptosis. Another laminin-derived peptide containing SIKVAV from the A chain has been found to increase tumor growth, lung and liver colonization, and angiogenesis as well as collagenase IV activity and plasminogen activation. This peptide was found to promote angiogenesis in an in vivo model by increasing the recruitment of neutrophils. This peptide also increases monocytic macrophage PGE2 and matrix metalloproteinase. Further screening of the G domain of laminin identified a peptide LQVQLSIR which increases melanoma metastases to the liver. Using this information and the newly developed models of human tumors, the development of new therapeutic strategies for cancer should be facilitated.